High Cooperativity in Negative Feedback can Amplify Noisy Gene Expression

Burst-like synthesis of protein is a significant source of cell-to-cell variability in protein levels. Negative feedback is a common example of a regulatory mechanism by which such stochasticity can be controlled. Here we consider a specific kind of negative feedback, which makes bursts smaller in t...

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Vydáno v:	Bulletin of mathematical biology Ročník 80; číslo 7; s. 1871 - 1899
Hlavní autoři:	Bokes, Pavol, Lin, Yen Ting, Singh, Abhyudai
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	New York Springer US 01.07.2018 Springer Nature B.V
Témata:	Algorithms Animals Bursting strength Cell Biology Coefficient of variation Computer Simulation Feedback Feedback, Physiological Gene Expression Humans Life Sciences Load Markov Chains Mathematical and Computational Biology Mathematical Concepts Mathematics Mathematics and Statistics Models, Genetic Negative feedback Original Article Protein biosynthesis Protein Biosynthesis - genetics Proteins Regulatory mechanisms (biology) Single-Cell Analysis Stochastic Processes Stochasticity Variation Asymptotic expansions Negative feedback 60K40 Stochastic gene expression Delayed production 41A60 Protein bursting 92C40
ISSN:	0092-8240, 1522-9602, 1522-9602
On-line přístup:	Získat plný text
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Popis
Shrnutí:	Burst-like synthesis of protein is a significant source of cell-to-cell variability in protein levels. Negative feedback is a common example of a regulatory mechanism by which such stochasticity can be controlled. Here we consider a specific kind of negative feedback, which makes bursts smaller in the excess of protein. Increasing the strength of the feedback may lead to dramatically different outcomes depending on a key parameter, the noise load, which is defined as the squared coefficient of variation the protein exhibits in the absence of feedback. Combining stochastic simulation with asymptotic analysis, we identify a critical value of noise load: for noise loads smaller than critical, the coefficient of variation remains bounded with increasing feedback strength; contrastingly, if the noise load is larger than critical, the coefficient of variation diverges to infinity in the limit of ever greater feedback strengths. Interestingly, feedbacks with lower cooperativities have higher critical noise loads, suggesting that they can be preferable for controlling noisy proteins.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	0092-8240 1522-9602 1522-9602
DOI:	10.1007/s11538-018-0438-y